Download Biochemistry/Proteins/Introduction

Biochemistry/Proteins/Introduction
Biochemistry/Proteins/Introduction
Protein role and importance
Proteins are among the fundamental molecules of biology. They are common to all life present on Earth today, and
are responsible for most of the complex functions that make life possible. They are also the major structural
constituent of living beings. According to the Central Dogma of Molecular Biology (proposed by Francis Crick in
1958), information is transferred from DNA to RNA to proteins. DNA functions as a storage medium for the
information necessary to synthesize proteins, and RNA is responsible for (among other things) the translation of this
information into protein molecules, as part of the ribosome.
Virtually all the complex chemical functions of the living cell are performed by protein-based catalysts called
enzymes. Specifically, enzymes either make or break chemical bonds. Protein enzymes should not be confused with
RNA-based enzymes (also called ribozymes), a group of macromolecules that perform functions similar to protein
enzymes. Further, most of the scaffolding that holds cells and organelles together is made of proteins. In addition to
their catalytic functions, proteins can transmit and commute signals from the extracellular environment, duplicate
genetic information, assist in transforming the energy in light and chemicals with astonishing efficiency, convert
chemical energy into mechanical work, and carry molecules between cell compartments.
Functions not performed by proteins
Proteins do so much that it's important to note what proteins don't do. Currently there are no known proteins that can
directly replicate themselves. Prions are no exception to this rule. It is theorized that prions may be able to act as a
structural template for other chemically (but not structurally) identical proteins, but they can't function as a native
template for protein synthesis de novo. Proteins don't act as fundamental energy reserves in most organisms, as their
metabolism is slower and inefficient compared to sugars or lipids. They are, on the other hand, a fundamental
nitrogen and amino acid reserve for many organisms. Proteins do not directly function as a membrane in most
organisms, except viruses; however, they are often important components of these structures, lending both stability
and structural support.
Proteins as polymers of aminoacids
Composition and Features
Proteins are composed of a linear (not branched and not forming rings) polymer of amino acids. The twenty
genetically encoded amino acids are molecules that share a central core: The α-carbon is bonded to a primary amino
(-NH2) terminus, a carboxylic acid (-COOH) terminus, a hydrogen atom, and the amino acid side chain, also called
the "R-group". The R-group determines the identity of the amino acid. In an aqueous solution, at physiological pH
(~6.8), the amino group will be in the protonated -NH3+ form, and the carboxylic acid will be in the deprotonated
-COO- form, forming a zwitterion. Most amino acids that make up proteins are L-isomers, although a few exotic
creatures use D-isomers in their proteins.
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Biochemistry/Proteins/Introduction
Amino acids polymerize via peptide bonds, which is a type of amide
bond. A peptide bond is formed upon the dehydration of the
carboxy-terminus of one amino acid with the amine terminus of a
second amino acid. The resulting carbonyl group's carbon atom is
directly bound to the nitrogen atom of a secondary amine. A peptide
chain will have an unbound amino group free at one end (called the
N-terminus) and a single free carboxylate group at the other end (called
the C-terminus).
The written list of the amino acids linked together in a protein, in
The structure of an amino acid.
order, is called its primary structure. By convention, peptide sequences
are written from N-terminus to C-terminus. This convention mimics the way polypeptides are synthesized by the
ribosome in the cell. Small polymers of less than 20 amino acids long are more often called peptides or polypeptides.
Proteins can have sequences as short as 20-30 amino acids to gigantic molecules of more than 3,000 aminoacids (like
Titin,a human muscle protein).
Genetically-Encoded Amino Acids
While there are theoretically billions of possible amino acids, most proteins are formed of only 20 amino acids: the
genetically-encoded (or more precisely, proteogenic) amino acids. Note that all amino acids except glycine have a
chiral center at their α-carbons. (Glycine has two hydrogens on its α-carbon, and therefore it is achiral.) Besides
glycine, all proteogenic amino acids are L-amino acids, meaning they have the same absolute configuration as
L-glyceraldehyde. This is the same as the S-configuration, with the exception of cysteine, which contains a sulfur
atom in its side chain, and so the naming priority changes. D-amino acids are sometimes found in nature, as in the
cell walls of certain bacteria, but they are rarely incorporated into protein chains.
The side-chains of proteogenic amino acids are quite varied: they range from a single hydrogen atom (as for glycine,
the simplest amino acid) to the indole heterocycle, as found in tryptophan. There are polar, charged and hydrophobic
amino acids. The chemical richness of amino acids is at the base of the complexity and versatility of proteins.
Post-Translational Modification
Many proteins contain amino acids with side-chains that are different from the proteogenic twenty. These are
produced by chemical modification of amino acid side-chains after the synthesis of a protein has completed. Many
reactions can occur on sidechains, but common ones are oxidation, acylation, glycosylation (addition of a glycan, or
sugar), and methylation.
The importance of protein structure
Generally speaking, the function of a protein is completely determined by its structure. Molecules like DNA, which
perform a fairly small set of functions, have an almost fixed structure that's fairly independent from sequence. By
contrast, protein molecules perform functions as different as digesting sugars or moving muscles. To perform so
many different functions, proteins come in many different structures. The protein function is almost completely
dependent on protein structure. Enzymes must recognize and react with their substrates with precise positioning of
critical chemical groups in the three-dimensional space. Scaffold proteins must be able to precisely dock other
proteins or components and position them in space in the correct fashion. Structural proteins like Collagen must face
mechanical stresses and be able to build a regular matrix where cells can adhere and proliferate. Motor proteins must
reversibly convert chemical energy in movement, in a precise fashion.
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Protein folding depends on sequence
As Anfinsen demonstrated in the 1960's, proteins acquire their structure by spontaneous folding of the polypeptide
chain into the minimal energy configuration. Most proteins require no external factors in order to fold (although
specialized protein exist in cells, called chaperones, that help other, misfolded, proteins acquire their correct
structure) — the protein sequence itself uniquely determines the structure. Often the whole process takes place in
milliseconds. Despite the apparent chemical simplicity of proteins, the vast number of permutations of twenty amino
acids in a linear sequence leads to an amazing number of different protein folds. Nevertheless, protein structures
share several characteristics in common: they are almost all built of a few secondary structure elements (short-range
structural patterns that are recurrent in protein structures) and even the way these elements combine is often repeated
in common motifs. Nonetheless, it is still impossible to know what structure a given protein sequence will yield in
solution. This is known as the protein folding problem, and it is one of the most important open problems in modern
molecular biology.
Protein denaturation
Proteins can lose their structure if put in unsuitable chemical (e.g. high or low pH ; high salt concentrations;
hydrophobic environment) or physical (e.g. high temperature, high pressure) conditions. This process is call
denaturation. Denatured proteins have no defined structure and, especially if concentrated, tend to aggregate into
insoluble masses. Protein denaturation is by no means an exotic event: a boiled egg becomes solid just because of
denaturation and subsequent aggregation of its proteins. Denatured proteins can sometimes refold when put again in
the correct environment, but sometimes the process is irreversible (especially after aggregation: the boiled egg is
again an example). It is finally the proteins which are responsible for susceptibility or resistance to a pathogen or
parasite.
Proteins can fold into domains
A significant number of proteins, especially large proteins, have a structure divided into several independent
domains. These domains can often perform specific functions in a protein. For example, a cell membrane receptor
might have an extracellular domain to bind a target molecule and an intracellular domain that binds other proteins
inside the cell, thereby transducing a signal across the cell membrane.
The domain of a protein is determined by the secondary structure of a protein there are four main types of domain
structures: alpha-helix, beta-sheet, beta-turns, and random coil.
The alpha-helix is when the poly-peptide chain forms a helix shape with the amino acids side chains sticking out,
usually about 10 amino acids long. The alpha-helix gets its strength by forming internal hydrogen bonds, that occur
between amino acid 1 and 4 along the length of the helix. A high concentration of Glycine's in a row tend towards
the alpha-helix conformation.
The beta-sheet structure is composed of poly-peptide chains stacking forming hydrogen bonds between the sheets.
You can from parallel sheets by stacking in the same direction N-C terminal on top of N-C terminal or form
anti-parallel by stacking in opposite directions N-C terminal on top of C-N terminal. Beta-turns link two anti-parallel
beta strands by a 4 amino acid loop in a defined conformation.
A random coil is a portion of the protein that has no defined secondary structure.
Domains of a protein then come from unique portions of the peptide that are made up of these types of secondary
structure.
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Article Sources and Contributors
Article Sources and Contributors
Biochemistry/Proteins/Introduction Source: http://en.wikibooks.org/w/index.php?oldid=2126478 Contributors: Brim, Cyclop, Geocachernemesis, Jguk, Jomegat, Lineweaver, Matzman,
Mike.lifeguard, Moleculesoflife, Pharamund, QuiteUnusual, Seldon, TreborA, Uncle G, 35 anonymous edits
Image Sources, Licenses and Contributors
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